MSc by Research: Bittersweet – the consequences of anti-diabetic drugs on immunity during infection

The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master’s degree. It is designed specifically to enhance your skills for a PhD or research career. If you have your own ideas for a research project in this area, we would love to hear from you! Please reach out to one of the project supervisors above to discuss your ideas. You can find further information about our academic requirements and MSc by Research programme structure here.

Fungal infections have increased substantially worldwide and is a significant cause of morbidity and mortality, especially among critically ill patients. Glucose homeostasis is critical for host outcomes during systemic Candida species infection. People with diabetes are more susceptible but it is also recognised that diabetes therapies enhance susceptibility to fungal infection. For example, in animal studies metformin lowers glucose levels and consequently immune cells depleted of glucose die. Similarly, SGLT2 inhibitors reduce reabsorption of glucose but in humans are associated with urinary tract fungal infections. We have recently shown that a potential therapy PTP1B inhibition increases the susceptibility to Candida albicans infection in experimental models where the fungus depletes glucose levels in susceptible organs. However, the exact immunometabolic molecular mechanisms underpinning how anti-diabetic medicines, despite their health benefits, can increase infection susceptibility and whether this is different in diabetic and non-diabetic conditions is lacking.

The key aim of this research project is to fully analyse and define the mechanisms by which anti-diabetic medicines influence the functions of the immune cells, neutrophils and macrophages that fight fungal infection, specifically:

1. What are the biological effects of anti-diabetic drugs on human neutrophil and macrophage function regarding their ability to engulf and kill invading fungal species?
2. What are the alterations in metabolism and intracellular signalling pathways in these immune cells, subsequently affecting functions relating to infection susceptibility?
3. Do anti-diabetic medicines change the efficacy of anti-fungal medicines and change the course and level of fungal infection?

To address these aims, the student will receive extensive training in our well-established infection models, neutrophil and human blood macrophage isolation and culture, multicolour flow cytometry, high powered confocal and real time imaging microscopy, fungal killing, antifungal susceptibility assays and phagocytosis assays and novel intracellular signalling analysis/metabolic profiling (Seahorse metabolic flux) and molecular biology techniques. A strong emphasis will be placed on training in experimental design, data analysis, data management, report writing and presentations. The studies will help inform future drug development as to the best preventative measures to protect against increased susceptibility of people with diabetes to C. albicans infection.

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Applicants to this project should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Informal enquiries are encouraged, please contact Professor Heather Wilson ([email protected]) for further information.

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APPLICATION PROCEDURE:

Please note: This is a self-funded opportunity.

• Prospective students should contact the lead supervisor (via the email address listed above) to discuss the research project and complete a proposal form prior to / or shortly after applying.
• Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
• You should apply for Medical Sciences (MSc) to ensure your application is passed to the correct team.
• Please clearly note the name of the supervisor and the project title on the application form. If this is not included, your application may not be considered for the project.
• Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree (or international equivalent) at undergraduate level.
• Your application must include: a personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
• If you are still undertaking your undergraduate degree, it is helpful to the selection panel if you could provide documentation showing your grades to date (this can be a screenshot from an online portal).
• Please note: Project supervisors will not respond to requests for funding assistance.
• If you require any additional assistance in submitting your application or have any queries about the application process, please don’t hesitate to contact us at [email protected]